Painful musculoskeletal diseases affect millions of Americans, and are associated with profound consequences such as disability and mortality. Increasing evidence suggests that part of the deleterious impact of pain may be mediated by inflammation, that pain and inflammatory processes engage in a dynamic, reciprocally-interacting relationship, and that cognitive and emotional factors are intimately involved in the experience of pain and its consequences. The present proposal will provide the necessary foundation to build a clinical research program elucidating the mechanisms by which psychosocial processes such as pain-related catastrophizing exert deleterious effects on pain-related outcomes in arthritis, fibromyalgia, and other painful musculoskeletal conditions. Catastrophizing has been identified as a set of negative cognitive and emotional processes in response to pain, and has been linked to central sensitization, reduced quality of life, and enhanced disease activity in the context of rheumatic pain. The PI for this proposal has a NIAMS Mentored Career Development Award to study rheumatoid arthritis;the present application would provide the necessary resources to investigate pro-inflammatory immune system responses to acute pain (and catastrophizing's impact on inflammatory responses to acute pain) not only in RA, but in other rheumatic disease groups as well. Participants will undergo sessions of quantitative sensory testing, during which painful mechanical and cold stimuli will be administered;individual and group differences in the magnitude and time course of neuroendocrine (i.e., cortisol) and pro-inflammatory cytokine (i.e., IL-6 and TNF-1) responses to acute pain will be studied. To our knowledge, this would be the first controlled study to evaluate catastrophizing's impact on inflammatory responses to acute noxious stimulation across multiple samples of patients with persistent pain. The need for further research into catastrophizing's mechanisms of action is increasingly important in the context of an epidemic of chronic pain. Epidemiological studies have identified catastrophizing as a risk factor for the development and persistence of pain, and reduction of pain-related catastrophizing represents an important goal for multidisciplinary pain treatment. The applicant's goal for the proposed project is to understand the pathways by which catastrophizing impacts pain-related outcomes in order to refine biopsychosocial models of pain and facilitate the enhancement of psychosocial interventions for chronic musculoskeletal pain. PUBLIC HEALTH RELEVANCE: Painful musculoskeletal diseases affect millions of Americans, and are associated with profound consequences such as disability and mortality. Increasing evidence suggests that part of the deleterious impact of pain may be mediated by inflammation, that pain and inflammatory processes engage in a dynamic, reciprocally-interacting relationship, and that cognitive and emotional factors are intimately involved in the experience of pain and its consequences. Epidemiological studies have identified catastrophizing as a risk factor for the development and persistence of pain, and reduction of pain-related catastrophizing represents an important goal for multidisciplinary pain treatment. The applicant's goal for the proposed project is to understand the pathways by which catastrophizing impacts pain-related outcomes in order to refine biopsychosocial models of pain and facilitate the enhancement of psychosocial interventions for chronic musculoskeletal pain.